Compositions and methods for enhancing brain function

ABSTRACT

A nutritional supplement composition enhances cognitive function and includes huperzine A, vinpocetine, acetyl-L-carnitine, and rhodiola. The composition is formulated for oral administration. The huperzine A, vinpocetine, acetyl-L-carnitine, and rhodiola are in a ratio a:b:c:d: respectively such that a as the huperzine A is between about 0.8 and 1.2, b as vinpocetine is between about 80 and 120, c as rhodiola is about 1,600 and 2,400, and d as the acetyl-L-carnitine is between about 8,000 and 12,000.

RELATED APPLICATION(S)

This application is a continuation-in-part application of U.S.application Ser. No. 13/307,587 filed Nov. 30, 2011, which is acontinuation-in-part application of U.S. application Ser. No.11/758,151, filed Jun. 5, 2007 (now U.S. Pat. No. 8,071,610), whichclaims priority to U.S. provisional application Ser. No. 60/803,943,filed Jun. 5, 2006, and U.S. provisional application Ser. No.60/820,201, filed Jul. 24, 2006, the disclosures which are incorporatedby reference herein.

FIELD OF THE INVENTION

The field of the invention is nutritional supplements and methodstherefore, especially as they relate to enhancers of cognition and mood.

BACKGROUND OF THE INVENTION

There are numerous approaches known in the art to enhance mood andcognitive performance in normal individuals, including pharmaceuticalinterventions, aerobic exercise and certain cognitive training programs.Recently, certain nutraceutical agents, such as, ginkgo biloba, andmulti-agent compounds have claimed cognitive enhancing effects.Unfortunately, most of those agents and compounds make claims based onmere inclusion of one or more individual ingredients whose clinicallydemonstrated efficacy level(s), or minimal therapeutic thresholdamount(s), are typically not achieved in the proposed multi-agentcompound.

In other examples, various supplements and formulations comprising amultiplicity of allegedly active ingredients are marketed as nootropics,or cognitive enhancing agents. For example, the commercially available“Focus Factor” formulation sports over 30 ingredients, while thecommercially available “Brain Lightning” formulation has nearly 20ingredients. Other formulations have been available recently. Suchformulations as marketed include multiple active ingredients withrespective specific effects, and therefore, often suggest that multipleactive ingredients will provide additive, or even synergistic beneficialeffects. There have been some clinical trails on some of these otherformulations and some improvements seen, but results have been mixed.Indeed, the beneficial effects of selected ingredients, whichindividually show cognitive benefits, but when combined may possiblyeven be canceled out by sensory or metabolic overstimulation. Forinstance, overstimulation of the cholinergic neurotransmitter system isknown to cause receptor desensitization and downregulation of density.

Moreover, the few isolated compounds claiming one or more cognitiveeffects that have been subjected to well controlled (e.g., randomized,double blind, placebo controlled) clinical trials in relativelysignificant sample sizes (e.g., >50) have only shown clinical effect inselected populations (e.g., an older population, cognitively impaired,abnormal, or low normal subpopulation), and may therefore have nosignificant effect in a healthy population of relatively wide age range.For example, certain conditions of compromised cognitive and moodfunction (e.g., chronic stress, sleep loss, depression, poor diet,aging) can be individually treated by targeting and addressing theunderlying neuro-chemical imbalance(s). For instance, a lack of certainB vitamins, such as, B-1 or B-12, or minerals, such as, magnesium orselenium, can induce low normal to impaired states of cognition. Suchnutritional supplementation can often restore partial or full cognitivefunctioning. In one example, Oakland intercity kids with extremely lowIQ status, were given a cocktail of certain vitamins and minerals andshowed an increase of over 10% in IQ points. In general, however, therehave been few if any qualified studies showing single or multi-agentcompounds positively and significantly effecting mood and cognitivestatus in a healthy, broad age range population.

Therefore, while numerous compositions and methods for cognitiveenhancement are known in the art, all or almost all of them suffer fromone or more disadvantages. Thus, there is still a need to provideimproved nootropic compositions and methods, for improvements in moodand cognitive function in both abnormal, low normal and normal highfunctioning general population groups.

SUMMARY OF THE INVENTION

The present invention is directed to compositions and methods ofenhancing mood and cognitive function in a human, and particularly toorally administered compositions. Especially preferred compositions havebeen clinically proven to increase selected aspects of mood andcognition and comprise a minimum number of active ingredients near, ator above their proven therapeutic threshold.

A nutritional supplement composition enhances cognitive function andincludes huperzine A, vinpocetine, acetyl-L-carnitine, and rhodiola.This composition is formulated for oral administration. The huperzine A,vinpocetine, acetyl-L-carnitine, and rhodiola are in a ratio a:b:c:drespectively such that a as the huperzine A is between about 0.8 and1.2, b as vinpocetine is between about 80 and 120, c as rhodiola isabout 1,600 and 2,400, and d as the acetyl-L-carnitine is between about8,000 and 12,000.

In one example, the composition includes a Vitamin B complex (e) in aratio a:b:c:d:e with the huperzine A, vinpocetine, acetyl-L-carnitine,and rhodiola such that (e) as the Vitamin B complex is between about 700and 1,200. In an example, the Vitamin B complex is formed as VitaminsB3, B5 and B6. In another example a green tea and guarana extract (f) isin a weight ratio a:b:c:d:f with the huperzine A, vinpocetine,acetyl-L-carnitine, and rhodiola such that (f) as the green tea andguarana extract is between about 1,600 and 2,400.

In an example, the rhodiola is formed of about 2 to 4% rosavins and 0.5to 1.5% salidrosides. In another example, the hyperzine A,acetyl-L-carnitine, vinpocetine, and rhodiola together account for atleast 80 wt % of a dosage unit of the composition. The huperzine A,vinpocetine, acetyl-L-carnitine, and rhodiola are in a ratio to eachother in another example such that the huperzine A is between about 0.9and 1.1, the vinpocetine is between about 90 and 110, the rhodiola isbetween about 1,800 and 2,200, and the acetyl-L-carnitine is betweenabout 9,000 and 10,000.

In another example, the acetyl-L-carnitine is present in an amount fromabout 1,250 mg to 1,500 mg, the vinpocetine is present in an amount fromabout 10 mg to 30 mg, the rhodiola is present in an amount from about250 mg to 350 mg, the hyperzine A is present in an amount from about 50mcg to 200 mcg, the green tea and guarana extract is present in anamount from about 250 mg to 350 mg, and the Vitamin B complex is presentin an amount from about 125 mg to 175 mg.

In another example, the composition is formulated with an entericcoating and an inactive ingredient may be selected from the groupconsisting of a carrier, a binder, an excipient, a dye and combinationsthereof. A method of assisting enhancement of cognitive function in aperson is also included by administering the nutritional supplementcomposition.

A nutritional supplement composition enhances cognitive function andincludes huperzine A, vinpocetine, acetyl-L-carnitine, rhodiola, aVitamin B complex comprising Vitamins B3, B5 and B6, and a green tea andguarana extract. The composition is formulated for oral administrationand the huperzine A, vinpocetine, rhodiola, acetyl-L-carnitine, each ofVitamins B3, B5 and B6, and the green tea and guarana extract are in aratio a:b:c:d:e:f respectively such that a as huperzine A is betweenabout 0.8 and 1.2, b as the vinpocetine is between about 80 and 120, cas the rhodiola is between about 1,600 and 2,400, d as theacetyl-L-carnitine is between about 8,000 and 12,000, e as each of theVitamins B3, B5 and B6 is between about 250 to 400, and f as the greentea and guarana extract is between about 1,600 and 2,400. Vitamin B3 isformed as Niacin and Niacinamide in one example and the Vitamin B5 isformed as pantothenic acid as a D-calcium pantothenate.

In yet another example, a nutritional supplement composition enhancescognitive function and includes huperzine A; vinpocetine;acetyl-L-carnitine; rhodiola; a Vitamin B complex comprising VitaminsB3, B5 and B6; and a green tea and guarana extract. The composition isformulated for oral administration and the huperzine A is present in anamount from about 50 mcg to 200 mcg, and the vinpocetine is present inan amount from about 10 mg to 30 mg. The rhodiola is present in anamount from about 250 mg to 350 mg, and the acetyl-L-carnitine ispresent in an amount from about 1,250 mg to 1,500 mg. Each of VitaminsB3, B5 and B6 are present in an amount from about 40 mg to 60 mg and thegreen tea and guarana extract are present in an amount from about 250 mgto 350 mg. The huperzine A, acetyl-L-carnitine, vinpocetine and rhodiolatogether account for at least 80 wt % of a dosage unit of thecomposition.

BRIEF DESCRIPTION OF THE DRAWINGS

Other objects, features and advantages of the present invention willbecome apparent from the detailed description of the invention whichfollows, when considered in light of the accompanying drawings in which:

FIG. 1 is a table showing the cognitive tests cited in the morecomprehensive report of testing of the Procera AVH composition set forthin the JANA article entitled, “A Randomized, Double-Blind, PlaceboControlled Study Examining the Effects of a Combination NutraceuticalFormula on Cognitive Functioning and Mood,” in accordance with anon-limiting example.

FIG. 2 is a table showing the means and standard deviations forsignificant outcome variables at baseline and again at 30 days for theProcera AVH composition and placebo groups in accordance with anon-limiting example.

FIG. 3 are graphs showing the numeric working memory accuracy and wordrecognition speed (long term memory) for the placebo and the Procera AVHcomposition in accordance with a non-limiting example.

FIG. 4 shows a bar chart of age-related improvements and speed of memoryretrieval with the composition in accordance with a non-limitingexample.

FIG. 5 are graphs showing the changes in mood variables for a placeboand the Procera AVH composition in accordance with a non-limitingexample.

DETAILED DESCRIPTION

The inventor has discovered that specific combinations of nutritionallysafe compounds have significant and desirable effect on cognitive andmood function while having a minimum number of active ingredients atproven minimal therapeutic threshold levels. Moreover, all of the activeingredients in contemplated compositions were selected to impact thelargest number of neuro-cognitive structures and functions in the humanbrain. Furthermore, contemplated compositions are effective for optimalimprovement of cognitive states and status ranging from normal todeclining more rapidly than normal, or accelerated stages of decline, topre-dementia states (e.g., MCI— mild cognitive impairment), and even MCIprecursor states (e.g., AAMI, or age-associated memory impairment).

It should be particularly appreciated that contemplated formulationsare, to the best of the inventor's knowledge, the first formulationsthat have been administered to a cognitively normal, or healthy, broadage range group and clinically shown to enhance attention (aka focus,concentration) short term working memory, memory consolidation andprocessing speed, mental clarity and energy, fluid intelligence, generalreasoning and executive functions and a broad range of moods (e.g., toreduce depressed states, anxiety, confusion, hostility and anger).Particularly, contemplated compositions have been demonstrated toimprove with high statistical significance numerical working memoryaccuracy (working memory), word recognition speed (long term memoryconsolidation), anger-hostility (mood), and total mood disturbance(mood).

Contemplated compositions have further substantially improved (to nearstatistical significance) spatial working memory accuracy (workingmemory), attention, depression (mood), confusion (mood), and vigor(mood).

In contrast, heretofore known nootropic formulations include a largerange of ingredients (e.g., U.S. Pat. No. 6,964,969 listing 47ingredients) with unknown interactions, wherein clinical information oncognitive enhancement was only available for isolated ingredients.Therefore, and as pointed out in more detail further below, the presumedeffect of such formulations was based on a summarization of knowneffects of individual ingredients, which is in most if not all casesinconsistent with the actual effect. On the other hand, certainsupplements have been tested and were found effective in a specificmanner (e.g., Eur. J. Pharmacol. 2000; 398(1):56-72 where improvement ofcognitive function in rats with chronic cerebral hypoperfusion isreported). As a consequence, these supplements are often marketed withunsubstantiated and/or overextended claims with regard to their allegedeffect on human cognition as the reported and specific effects oftenfail to translate into specific and measured advantages in human.

In one exemplary and preferred formulation, a nutritional supplement orpharmaceutical composition is prepared that includes a therapeuticallyeffective daily dosage of acetyl-L-carnitine (preferably 1250-2000 mg/d,and even more preferably 1500 mg/d), vinpocetine (preferably 10-30 mg/d,and even more preferably 15 mg/d) or rhodiola extract (also referred toherein as ‘rhodiola’, preferably standardized to 3% rosavins and 1%salidroside, and most preferably 250-350 mg, and most preferably about300 mg), and huperzine A (preferably 50-200 mcg/d, and even morepreferably 150 mcg/d). Additionally, such formulations may furtherinclude alpha lipoic acid (preferably in an amount of 300-500 mg, mostpreferably about 400 mg as a daily dosage), rhodiola (preferably in anamount of 200-400 mg, most preferably about 300 mg as a daily dosage),and biotin (preferably in an amount of 400-600 mcg, most preferablyabout 500 mcg as a daily dosage). The following table illustratesexemplary compositions.

Formulation I Formulation II Acetyl-L-carnitine 1,500 mg 1,500 mg Vinpocetine 15 mg (or rhodiola)  15 mg Huperzine A   150 mcg  150 mcgAlpha lipoic acid —/— 400 mg Biotin —/—  500 mcg Rhodiola 300 mg (orvinpocetine) 300 mg

Here, Formulation I has as alternative ingredients vinpocetine andrhodiola, and based on unpublished considerations and observations, bothversions of Formulation I are deemed to be equivalent with respect tothe biological effects. Moreover, it is also contemplated that Formula Ican include both, vinpocetine and rhodiola. Such formulation is expectedto have increased benefits in the mood measures in addition to thebenefits for Formula I without rhodiola. Formulation II is also known asProcera, while Formulation II is also known as Ceretrophin. Experimentaldata for both Formulations are provided in the experimental sectionbelow.

It is also possible to use ginko biloba with or in addition to or insubstitution of the vinpocetine if vinpocetine is not availablecommercially. There were past instances when vinpocetine was not readilyavailable commercially, and thus, rhodiola could be used as a substitutein Formulation I as a possibility. Rhodiola has been known to havepleiotropic properties and have multiple mechanisms of action.

Most preferably, the effective daily dosage is administered between oncedaily and four times daily in dosage units of accordingly adjustedweight. While not limiting to the inventive subject matter,acetyl-L-carnitine in contemplated formulations is thought to increasecerebral energy metabolism by assisting in mitochondrial beta-oxidationand to donate an acetyl moiety for synthesis of acetylcholine, whileVinpocetine (several other unique mechanisms of action, includinganti-inflammatory at microglial level) is thought to dilate bloodvessels in the brain, as well as improve red blood cell deformability,to thus allow for better perfusion into and throughout neuro-cognitiveregions and structures of the brain. Vinpocetine is known as a potentanti-inflammatory agent and its anti-inflammatory action is believed tobe caused by a direct inhibition of the IkB kinase complex (IKK) ratherthan PDE blockage. It also inhibits subsequent induction ofproinflammatory mediators and multiple cell types, including vascularsmooth muscle cells, endothelial cells, microphages, and epithelialcells. It also inhibits monocyte adhesion and chemotaxis, which arecritical processes during inflammation. Further details are found in thearticles entitled: “Vinpocetine as a Potent Antiinflammatory Agent,”PNAS, Jun. 1, 2010, Vol. 107, No. 22, pages 9921-9922; and “VinpocetineInhibits NF-kB-Dependent Inflammation via an IKK-Dependent butPDE-Independent Mechanism,” PNAS, May 25, 2010, Vol. 107, No. 21, pages9795-9800, the disclosures which are hereby incorporated by reference intheir entirety.

Huperzine A is thought to act as an acetylcholine esterase inhibitor andantioxidant, as well as other neuroprotective effects including NMDAreceptor antagonism and the downregulation of glutamate induced calciummobilization and excitotoxiciy. Huperzine A is isolated from the Chineseherb Huperzia serrata and is a potent, highly specific and reversibleinhibitor of acetylcholinesterase. It has been found to reverse orattenuate cognitive deficits in a broad range of animal models. Clinicaltrials in China have demonstrated that Huperzine A significantlyrelieves memory deficits in aged subjects, patients with benignsenescent forgetfulness, Alzheimer's disease (AD) and vascular dementia(VD), with minimal peripheral cholinergic side effects compared withother AChEIs in use. Huperzine A possesses the ability to protect cellsagainst hydrogen peroxide, β-amyloid protein (or peptide), glutamate,ischemia and staurosporine-induced cytotoxicity and apoptosis. Theseprotective effects are related to its ability to attenuate oxidativestress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53and caspase-3, protect mitochondria, and interfere with APP metabolism.Antagonizing effects on NMDA receptors and potassium currents maycontribute to the neuroprotection as well. It is also possible that thenon-catalytic function of AChE is involved in neuroprotective effects ofHuperzine A. The therapeutic effects of Huperzine A on AD or VD areprobably exerted via a multi-target mechanism.

Therefore, and viewed from a different perspective, contemplatednutritional supplements for enhancing cognitive function include (a)huperzine A, (b) one of vinpocetine and Rhodiola, and (c)acetyl-L-carnitine, wherein (a) and (b) and (c) are present in a ratioof x:y:z, wherein x is between 0.8 and 1.2, y is between 80 and 120 forvinopcetine and between 1,600 and 2,400 for rhodiola, and z is between8,000 and 12,000. In such methods, the supplements may include theadditional ingredients (i) alpha lipoic acid, (ii) Rhodiola where (b) isvinpocetine, and (iii) biotin. In another step, the supplement ispreferably formulated for oral administration such that the huperzine A,vinpocetine, and acetyl-L-carnitine together account for at least 80 wt% of a dosage unit of the supplement, or such that the additionalingredients (i), (ii), and (iii) and the huperzine A, vinpocetine, andacetyl-L-carnitine together account for at least 80 wt % of a dosageunit of the supplement. Viewed from a different perspective, huperzine Amay present in an amount of about 150 mcg, vinpocetine may be present inan amount of about 15 mg or rhodiola may be present in an amount ofabout 300 mg, and/or acetyl-L-carnitine may present in an amount ofabout 1,500 mg. Additionally, it is typically preferred that the alphalipoic acid is present in an amount of about 400 mg, Rhodiola is presentin an amount of about 300 mg where vinpocetine is present, and biotin ispresent in an amount of about 500 mcg. As used herein, the term “about”in conjunction with a numeral refers to a range of that numeral+/10%,inclusive. Biotin may protect against its known depletion by alphalipoic acid.

Where desired, optional additional active ingredients may be added, andespecially contemplated include folic acid (typically in an amount of atleast 0.1 mg per dosage unit, and more preferably at least 1 mg perdosage unit) or potassium (typically in an amount of at least 10 mg perdosage unit, and more preferably at least 100 mg per dosage unit).Furthermore, contemplated supplements may include inactive ingredients,which may help in formulation, disintegration, or other manner.Therefore, suitable inactive ingredients include carriers, binders,excipients, dyes, etc. Oral formulation is typically in form of a liquidor powder, or gel, or a solid form, and most preferably in form oftablet, pill, dragee, capsule, or softgel which may or may not have anenteric coating, such coating allowing for the ingredients to by-passthe upper GI tract where gastro-intestinal disturbances can beproblematic for some individuals. Moreover, one or more of the activeingredients may be in slow release formulation to extend release over aperiod of between 1-24 hours. In less preferred aspects, the supplementmay also be formulated as a liquid or a gel, or embedded in adissolvable film or chewing preparation.

It is further preferred that the supplement is formulated such that thedaily dosage unit of the supplement is equal or less than 1,200 mg, morepreferably equal or less than 1,600 mg, and even more preferably equalor less 2,000 mg, and most preferably equal or less than 2,400 mg,wherein administration may be between once daily and ten times daily.Therefore, suitable oral single dosage forms may preferably have aweight between 200 mg and 600 mg. Regardless of the actual weight of thesingle dosage form, it is preferred that the huperzine A, vinpocetine,and acetyl-L-carnitine together account for at least 80 wt %, morepreferably at least 85 wt %, even more preferably at least 90 wt %, andmost preferably at least 95 wt % of a dosage unit of the supplement, orwherein the additional ingredients (i), (ii), and (iii), and thehuperzine A, vinpocetine, and acetyl-L-carnitine together account for atleast 80 wt %, more preferably at least 85 wt %, even more preferably atleast 90 wt %, and most preferably at least 95 wt % of a dosage unit ofthe supplement.

With respect to marketing such compositions it is contemplated that thesupplement may be associated with an information (e.g., printed,displayed, or audio) stating that the nutritional supplement enhancesattention, short term working memory, memory recall capacity and memoryrecall speed, mental clarity, mental energy, speed of processing, fluidintelligence, and/or mood. Most preferably, such statement is includedon a packaging label. Furthermore, contemplated supplements may beprovided with an interactive tool (e.g., computer software, link, flashcards, electronic device, etc) that allows for testing, training, and/orvalidation of the cognitive enhancement or that allows for validation ofefficacy of the supplement and/or proper personal dosing, or titrationof the supplement to achieve optimal efficacy.

Consequently, a method of assisting enhancement of cognitive function ina person using a nutritional supplement includes a step of providingcontemplated compositions for oral administration under a schedule andprotocol effective to improve cognitive function (with respect to thecomposition of the supplement, the same considerations as describedabove apply). Most typically, the cognitive function is a function ofone or more types of memory including immediate, short term (a/k/aworking memory) and long term (aka episodic, delayed) memory includingsensory, procedural, verbal, semantic, numeric, visual, spatial andobject learning and recall, a function of memory processing speed,consolidation and retrieval, an aspect of mood, a function of attention(aka focus and concentration), a function of fluid intelligence andprocessing speed, an executive function, e.g., decision making,multi-tasking (aka task shifting, or switching) and general reasoning.As already pointed out above, the supplement may be provided with aninteractive tool that allows at least one of validation of efficacy ofthe supplement and proper personal dosing, or titration of thesupplement.

EXPERIMENTS Clinical Study Results of Inventive Composition vs.Comparative Composition

In the following, the composition according to the inventive subjectmatter is referred to as Procera, while the second composition wastermed comparative composition. Most notably, Procera producedsignificant widespread, global cognitive effects in short term memory,working memory, and longer term memory consolidation and speed ofprocessing measures. What's more, test subjects displayed improvement ina range of mood measures including depression, anxiety, anger andhostility, and exhibited more mental vigor, confidence and clarity.

This first section of experiments and methods and results were initialstudies while a more comprehensive set of the tests and results as partof that original test are set forth below also and taken from thearticle about this clinical trial entitled, “A Randomized, Double-Blind,Placebo Controlled Study Examining the Effects of a CombinationNutraceutical Formula on Cognitive Functioning and Mood,” published inthe Journal of the American Nutraceutical Association (JANA), Vol. 12,No. 1, 2009, pages 12-19, the disclosure which is hereby incorporated byreference in its entirety.

It should further be appreciated that the study was conducted withcognitively normal male and female subjects ranging in age from 22-66.Producing an overall effect in such a large demographic group isunexpected. Rather, it could be expected that the type of formulationused herein would only show significant improvements in either aslightly to moderately impaired group and an older group (e.g., age 45plus), where many conditions of aging and lifestyle factors contributeto an accumulated buildup of neurotoxic factors (e.g., free radicalinduced oxidative stress, heavy metals, cerebral vascular plaques,including beta amyloid plaques implicated in Alzheimer's, reducedcerebral vascular blood flow and glucose metabolism, calciumdyshomeostasis and others).

Procera Composition (Daily Dose in mg) Huperzine A 0.15 Vinpocetine 15Acetyl-L-Carnitine 1500

Comparative Composition (Daily Dose in mg) Huperzine A 0.15 Vinpocetine20 Acetyl-L-Carnitine 1000 Pantothenic Acid 250 DMAE 300 Thiamin 100Niacin (niacinamide) powder 250

As can be seen, the comparative composition employs similar butsignificantly distinct amounts of huperzine A, vinpocetine, andacetyl-L-carnitine, and further includes four active ingredients knownto have certain cognitive effects as isolated compounds, and purportedto act synergistically with the cholinergic-enhancing effects ofacetyl-l-carnitine and Huperzine A.

Methods

Participant Selection Criteria; Selection criteria includes those: (1)Not currently taking prescription drugs affecting the brain or nervoussystem (e.g., Modafinil, acetylcholinesterase inhibitors,anti-cholinergics, stimulants, L-dopa, MAO inhibitors, NMDA receptorantagonists, methylphenidate, amphetamine, pseudo-ephedrine, SSRIs andother anti-depressant medication); (2) Not currently taking OTCmedications affecting the brain (e.g., ephedra based diet pills); (3)Who have not used any supplements within the past 30 days that have aneffect on cognitive function, memory, anxiety, depression (e.g. Ginseng,Gingko, Vinpocetine, 5HTP, Tryptophan, St. John's Wort, ephedrine(ephedra), alpha GPC, Citicoline, phosphatidylserine,acetyl-L-carnitine, Focus Factor™; (4) Not active Smokers; (5) Nottaking the following: anti-coagulant drugs (Warfarin, Heparin, Plavix);anticholinergics or acetylcholinesterase inhibitors (bethanechol(Ureholine), donepezil (Aricept), rivastigmine (Exelon), galantamine(Reminyl), edrophonium (Enoln, Reversol, Tensilon), neostigmine(Prostigmin); (6) Do not have any of the following health conditions:AIDS, HIV; Chronic Fatigue Syndrome, Epstein Barr, Fibromylagia, Lupis,Multiple Sclerosis, Thyroiditis, Ulcerative Colitis, Crohn's Disease,Irritable Bowel Syndrome, dementia including Alzheimer's and Parkinsons'disease, Type 1 or 2 Diabetes, Insomnia or Sleep Apnea, Narcolepsy; (7)No history of head trauma; (8) No neurological deficits; (9) Notpregnant or lactating; (10) Not anticipating any planned changes inlifestyle (e.g. exercise regimen) for the duration of the study; (11) Noknown allergies to nuts.

In the initial methodology and results, 90 healthy participants betweenthe ages of 22-66 years of age were tested in treatment and placebogroups (total number of participants is n=100). A drop out rate(voluntary and non-voluntary withdrawal) of approximately 20% wasexpected and therefore additional participants were recruited for thestudy. The above-identified and incorporated by reference JANA articlesets forth more detailed results from the trial and explains that thecombination nutraceutical formula included the huperzine A, vinpocetine,and acetyl-L-carnitine and was examined in a 30-day, double blind,placebo controlled clinical trial and assessed a range of cognitive andmood variables. As noted in the article, seventy-four (74) healthyparticipants completed the study, with 43 in the combinationnutraceutical formula group, and 31 in the placebo group, and a mean ageof 48 years. The data from that trial is explained below and providesevidence that the composition proves a range of cognitive and moodvariables that were observable using a highly standardized and reliablebattery of cognitive tasks. The mood changes were readily observed andreported by the participants. The composition improves functioningduring complex cognitive tasks that assess memory such as working andlong term or consolidation rather than in simple discrimination taskssuch as choice reaction time. The cognitive processes that appear to beimproved relate to the various stages of working memory processesincluding the initial (information) registration (i.e., forming a“memory trace”), the further consolidation of information into memorystores and the later stages of memory retrieval. This may suggest aspecific focus of effect on the human brain and incorporating frontaland temporal circuits that underpin working memory and long term memoryconsolidation and retrieval. Mental clarity and mental energy appear tobe improved most likely modulated by increased neurotransmitterfunction, cerebral metabolism and mitochondrial energetics.

The study as initially set forth was advertised in Melbourne newspapers,on community notice boards, the Brain Sciences Institute website, andvia the Brain Sciences to Institute database of interested participants.All interested individuals were screened over the phone by the researchnurse to assess their suitability for participation in the study.Subjects participated in periodic evaluation of their cognitivefunctions including memory, mood, energy and mental status by taking abattery of computerized tests and written questionnaires that assessedtheir cognitive functions which including attention, memory, executivefunction, mood, energy, stress level, state of mind and IQ.

The following neuropsychological tests were employed in the currentsstudy:

(1) The Cognitive Drug Research measure (CDR) is a well-validated test,which was used to assess attention, working memory and episodicsecondary (longer term memory, or consolidation). (2) Inspection time(IT) is a measure speed of early information processing. (3) The Profileof Mood States (POMS) is a self-report designed to measure sixdimensions of mood: tension-anxiety; depression-dejection;anger-hostility; vigor-activity; fatigue-inertia; andconfusion-bewilderment. (4) IQ was assessed using the Raven'sProgressive Matrices. This was done by administering the even items atbaseline and the odd items at Week 4. (5) The UWIST Mood AdjectiveChecklist was used to measure mood states and energy levels. (6) TheSpielberger State-Trait Anxiety Inventory is a 20-item questionnaire, tomeasure anxiety at the time of testing. (7) Perceived Stress Scale wasused to measure stress symptoms and effective coping.

Participants visited Swinburne University on 3 separate occasions 1)Visit 1: Health assessment, practice, baseline and acute testing 2)Visit 2: 1 week (7 days) following baseline testing and 3) Visit 3: 4weeks (28 days) following baseline testing. During the first visit,participants completed a general health assessment and were thenallocated into one of three treatment groups for baseline and acutetesting. Timeline for each testing period:

Baseline and Acute Testing

Baseline testing: 1. General health assessment: blood pressure, height,weight; 2. Random allocation of participants into one of the threetreatment groups; 3. CDR practice testing which is required in order tobecome familiar with the tests and what is required of participants; 4.CDR baseline testing; 5. Mood and energy scales will beadministered—POMS, STAI, UWIST mood adjective checklist, PSS and Raven'sMatrix.

Acute testing: 6. Groups were administered an initial dose of 2 tabletsalong with a snack of a peanut butter sandwich for adequate absorptionof fat-soluble ingredients and minimization of gastric distress from theconsumption of acetyl-L-carnitine. 7. 30 mins after initial dose of 2tablets, a second dose of 2 tablets was administered again with a snackas in step 5. 8. Following 60 minutes after the second dose (90 minutesafter initial dose) participants performed CDR testing. Participantswere then asked to take the appropriate number of tablets per day for 4weeks (28 days) according to their assigned treatment group. Allparticipants were asked to visit Swinburne University for a re-test atweek 1 and at the completion of the treatment period at week 4. Subjectswere given a Symptom Checklist to take home to monitor for any sideeffects and symptoms that they experience on a weekly basis.

Testing sessions 2 and 3 (1 and 4 weeks following baseline testing;Total time=approx 50 minutes): 1. CDR, Inspection Time and Raven'smatrix (week 4 only). 2. Mood and energy scales will beadministered—POMS, STAI, UWIST mood. Adjective checklist, PSS; 3.Participants submitted weekly symptom checklist 4. General healthassessment.

We used alternate forms of psychometric tests to reduce practice effectsas much as possible and to maximize the power of the study. Generalhealth assessments were undertaken by the BSI research nurse. Testingsessions were consistent on each testing day. Participants wererequested not to have alcohol or caffeine-containing food or beverageson the testing days (e.g., coffee, tea, chocolate and energy drinkscontaining caffeine or guarana). Further to control for food intakeparticipants they were also required to eat a light breakfast (e.g., 2pieces of toast or cereal with juice) on the testing days.

Results Cognitive Measures

Simple Reaction Time: The speed of simple reaction time did notsignificantly improve due to the Procera treatment across the 4 weeks ofadministration. This is the simplest cognitive measure in the cognitivebattery.

Digit Vigilance and Choice Reaction Time: These measures were excludedfrom analysis because of the large number of participants who reached100% accuracy at baseline serving to cause these variables to show aceiling effect. This effect significantly reduces the variance inmeasures and invalidates parametric (statistical) testing ofdifferences. Conceptually it is pointless to examine an effect ofimprovement from baseline to time two if the majority of the sample hasalready reached perfect performance at baseline.

Spatial Working Memory: There was a trend towards significance forSpatial Working Memory Accuracy (p=0.17). Although not significant, theresults (see mean values below) indicate that there was more of animprovement in accuracy over the treatment duration for the Procera thanfor the placebo. Larger sample size may help this result becomestatistically significant. This result should be treated as apreliminary finding that should be subjected to replication in a largersample.

Std. Condition Mean Deviation N Spatial Working Procera AVH 94.72228.53099 36 Memory New Stimuli- Placebo 96.6071 5.27987 28Accuracy-baseline Total 95.5469 7.29847 64 Spatial Working 97.08335.52591 36 Memory New Stimuli- Placebo 97.1429 5.51573 28 Accuracy-Week4 Total 97.1094 5.47757 64

There was also a trend towards statistical significance (p=0.09) for thenumber of outliers during the spatial working memory task. Outliersindicate lapses in concentration over the duration of the task. As canbe seen in the table below, participants in the Procera treatment groupshowed less mean number of such lapses during the task and weretherefore better able to focus and concentrate/process during thespatial working memory task which is a complex cognitive task.

Std. Condition Mean Deviation N Spatial Working Memory- Procera AVH1.0256 1.03840 39 Outliers-baseline Placebo .7813 .83219 32 Total .9155.95139 71 Spatial Working Memory- Procera AVH .7179 1.02466 39Outliers-week 4 Placebo .9063 1.20106 32 Total .8028 1.10350 71

Numerical Working Memory: Participants on the Procera treatment showedstatistically significant improvement (p=0.03) in Numerical WorkingMemory Accuracy compared to placebo participants. A statisticallysignificant improvement in holding numbers in working memory (immediatememory) was shown from Baseline to Week four due to the Proceratreatment.

Std. Condition Mean Deviation N Numeric Working Memory Procera AVH93.7653 5.14656 36 Original Stimuli-Accuracy- Placebo 95.7787 5.26386 30baseline Total 94.6805 5.25784 66 Numeric Working Memory Procera AVH95.4333 3.39970 36 Original Stimuli-Accuracy- Placebo 95.0380 3.94556 30week 4 Total 95.2536 3.63433 66

Picture Recognition: There was no significant change in performance inPicture Recognition over the 4 week trial attributable to either Placeboor Procera treatment.

Word Recognition: Word Recognition Accuracy improved for the Proceraparticipant group but decreased for the Placebo participant group acrossthe 4 weeks of the trial. Although this approached statisticalsignificance (p=0.12) this results suggests that Procera improves theaccuracy of memory consolidation of words.

Std. Condition Mean Deviation N Word Recognition Procera AVH 73.333616.25226 36 Original Stimuli- Placebo 74.2534 14.87757 19Accuracy-baseline Total 73.7440 15.54023 65 Word Recognition Procera AVH75.1853 15.50148 36 Original Stimuli- Placebo 73.1038 14.19566 29Accuracy-week 4 Total 74.2566 14.85472 65

Word Recognition: The speed of performance during the Word Recognitiontask was significantly improved (p=0.02) for participants on the Proceratreatment compared to the placebo treatment over the 4 weeks ofadministration. This indicated that Procera significantly improvedmemory consolidation processes and in particular the speed at which aparticipant was able to consolidate and access new memories into longterm storage.

Std. Condition Mean Deviation N Word Recognition Original Procera AVH853.1267 184.99467 36 Stimuli-Speed: Mean- Placebo 774.9913 122.44679 30basline Total 817.6106 163.26059 66 Word Recognition Original ProceraAVH 757.5228 138.40862 36 Stimuli-Speed: Mean- Placebo 750.5463147.03377 30 week 4 Total 754.3517 141.32551 66

Inspection Time: A small sub set of participants completed this task. Nodifferences were observed between the Procera and placebo groups butthis may be due to the low sample size.

Raven Progressive Matrices: Participants in the Procera group scoredstatistically higher (p=0.02) on the Raven Progressive Matrices at theend of the 4 week trial than did placebo participants, The Placebo andProcera group were not statistically different at baseline suggestingthat 4 week administration of Procera improves general reasoning, visualproblem solving and object working memory. This result supports theimprovement in spatial and numerical working memory shown in the trial.

Std. Std. Error Condition N Mean Deviation Mean Raven's- Procera AV 3011.1000 2.57776 .47063 advance progressive Placebo 22 10.5000 2.54015.54156 matrix- baseline Raven's- Procera AV 30 11.2667 3.24763 .59293advance progressive Placebo 24 9.4167 3.38689 .69135 matrix-w 4 Raven's-Procera AV 33 21.3030 5.74176 .99951 advance progressive Placebo 2618.4615 6.09413 1.19516 matrix-T

It should be noted that the Raven Progressive Matrices Set that wasadministered to both groups at 4 weeks was significantly harder than theset administered to the two groups at baseline.

Mood Measures Depression (p=0.06): The Procera group showed a decreasein depression scores relative to the placebo group. This suggests thatProcera may improve depressive mood.

Std. Treatment Mean Deviation N depression dejection Procera AVH 8.00009.42388 43 baseline (POMS) Placebo 5.1935 8.54174 31 Total 6.82439.11172 74 depression dejection Procera AVH 4.3256 5.12566 43 Week 4(POMS) Placebo 4.3548 6.57038 31 Total 4.3378 5.73209 74

Vigor (p=0.10): The Procera group showed an improvement in Vigor overthe 4 weeks of the trial relative to the placebo group.

Std. Treatment Mean Deviation N vigor baseline (PDMS) Procera AVH 18.1405.4711 43 Placebo 17.581 6.5359 31 Total 17.905 5.9037 74 vigor Week 4(PDMS) Procera AVH 19.5116 6.38589 43 Placebo 17.2903 6.72901 31 Total18.5811 6.57935 74

Anger Hostility (P<0.03): The Procera group showed a statisticallysignificant decrease in anger-hostility over the 4 week trial relativeto the placebo group. This indicates that 4 week treatment with Procerasignificantly improves feelings of anger and hostility. This result issupportive of the decrease in depression scores.

Std. Treatment Mean Deviation N anger hostility baseline Procera AVH7.8372 7.56222 43 (POMS) Placebo 4.4839 5.80730 31 Total 6.4324 7.0382174 anger hostility Week 4 Procera AVH 4.1628 4.30907 43 (POMS) Placebo3.8065 6.12329 31 Total 4.0135 5.11108 74

Confusion (p=0.06): Participants in the Procera group also showed adecrease in confusion over the 4 week trial which was greater than theplacebo participants. Again this result is consistent with the decreasein depression and anger hostility shown by the Procera participants overthe 4 week trial.

Std. Treatment Mean Deviation N confusion baseline (POMS) Procera AVH8.9302 4.74791 43 Placebo 7.5806 3.42320 31 Total 8.3649 4.27024 74confusion Week 4 (POMS) Procera AVH 6.1628 3.01528 43 Placebo 6.51613.94859 31 Total 6.3108 3.41602 74

Total Mood Disturbance (p=0.02): Participants in the Procera groupshowed a highly statistically significant reduction in mood disturbanceover the 4 week duration of the trial relative to the placeboparticipants. This result indicates that 4 week Procera treatment ishighly beneficial for improving mood.

Std. Treatment Mean Deviation N Total mood disturbance Procera AVH65.9302 30.50870 43 score BL (POMS) Placebo 52.9032 23.86120 31 Total60.4730 28.48466 74 Total mood disturbance Procera AVH 47.5581 17.1690543 score Week 4 (POMS) Placebo 46.5161 26.53158 31 Total 47.121621.42777 74

Procera Study Summary

The initial results of this study clearly indicate that contemplatedformulations of Huperzine, Vinpocetine, and Acetyl-L-Carnitine improveboth cognition and mood in healthy participants aged 25-60 years.Statistically significant improvements in several variables relative toplacebo could be attributed to the 4 week administration of Procera, andparticularly Numerical Working Memory Accuracy (working memory), WordRecognition Speed (long term memory consolidation), Anger-Hostility(mood), Total Mood Disturbance (mood), and Raven Progressive Matrices(fluid intelligence, general reasoning and spatial and object workingmemory). Placebo was a sugar pill.

The study also found some evidence approaching statistical significanceof the following measures to be improved due to the 4 week Proceratreatment: Spatial Working Memory Accuracy (working memory), Depression(mood), Confusion (mood), and Vigor (mood).

FIGS. 1-5 are various figures showing the cognitive tests and outcomevariables and results from the more complete clinical trial in the JANAincorporated by reference article. FIG. 1 shows cognitive tests used intesting and FIG. 2 shows the means and standard deviations forsignificant outcome variables at baseline. FIGS. 3-5 show various testresults as explained below.

There now follows further details and the more complete analysis of theoriginal Swinburne University Study identified above and now explainedin greater detail below.

Participants: Ninety participants (45 in each of the two groups) wereinitially enrolled into the 30 day chronic study. Seventy-four (74)participants completed the 30 days and were tested at both baseline andat 30 days (43 in the combination nutraceutical formula group and 31 inthe control group). The mean age of the combination nutraceuticalformula group was 49.5 years (SD=1.6 22-66 years) and the mean age ofthe placebo group was 47.1 years (SD=1.9 24-62) years. There was nosignificant difference in the number of males or females whoparticipated in the study.

Inclusion/Exclusion Criteria: Each participant underwent an individualscreening appointment with a registered nurse. Screening incorporated amedical history and cognitive assessment. Participants were eligible ifthey were aged between 22 and 66 years of age. Exclusion criteriaincluded the following: not currently taking prescription drugsaffecting the brain or nervous system (e.g., Modafinil,acetylcholinesterase inhibitors, anticholinergics, stimulants, L-dopa,MAO inhibitors, NMDA receptor antagonists, methylphenidate, amphetamine,pseudo-ephedrine, SSRIs and other anti-depressant medication); notcurrently taking OTC medications affecting the brain (e.g., ephedrabased diet pills); those who have not used any supplements within thepast 30 days that have an effect on cognitive function, memory, anxiety,depression (e.g. Ginseng, Gingko, Vinpocetine, 5HTP, Tryptophan, St.John's Wort, ephedrine (ephedra), alpha GPC, Citicoline,phosphatidylserine, acetyl-l-carnitine, Focus Factor™); not activesmokers; not taking the following: anti-coagulant drugs (Warfarin,Heparin, Plavix); anti-cholinergics or acetylcholinesterase inhibitors(bethanechol, Ureholine), donepezil (Aricept), rivastigmine (Exelon),galantamine (Reminyl), edrophonium (Enoln, Reversol, Tensilon),neostigmine (Prostigmin); do not have any of the following healthconditions: AIDS, HIV, chronic fatigue syndrome, Epstein-Barr,fibromyalgia, lupus, multiple sclerosis, thyroiditis, ulcerativecolitis, Crohn's disease, irritable bowel syndrome, dementia includingAlzheimer's and Parkinson's disease, Type 1 or 2 diabetes, insomnia orsleep apnea, narcolepsy; no history of head trauma; no neurologicaldeficits; not pregnant or lactating; not anticipating any plannedchanges in lifestyle (e.g. exercise regimen) for the duration of thestudy; and no known allergies to nuts.

Study Design: The study was a randomized double blind placebo-controlleddesign in which participants were allocated either a daily dose of thecombination nutraceutical formula or placebo for 30 days. The dose was1,515 mg per day and each participant was instructed to take 4 pills perday. The combination nutraceutical formula was the Procera AVH.

Measures: Several cognitive and psychological measures were assessed atbaseline and at 30 days.

Cognitive Testing: The CDR® program is an automated computerizedcognitive assessment system, which has been used in more than 250published clinical drug studies. The CDR system comprises a battery ofcognitive tests that are sensitive to the effects ofpsychopharmacological substances. The CDR system profiles and assesses arange of cognitive functions, including attention, informationprocessing, sub-loops of working memory, reasoning, secondary memory andskilled coordination. All tasks in the battery are computer controlled,with information being presented on high-resolution monitors, and theresponses recorded via a response module containing two buttons, onemarked ‘YES,’ the other marked ‘NO.’ The versions of the tests specifiedfor elderly participants were employed. The selected battery took theparticipants around 30 minutes to complete and parallel forms of thetasks were presented at subsequent testing sessions. The cognitive testsused from the battery are presented in the table of FIG. 1. The Profileof Mood States (POMS) is a self-report designed to measure sixdimensions of mood: tension/anxiety; depression/dejection;anger/hostility; vigor/activity; fatigue/inertia; andconfusion/bewilderment.

Procedure: At baseline each participant completed a general healthassessment, which included blood pressure, height and weight, and werethen randomly allocated into one of the two treatment groups. They thencompleted a CDR practice session, which is required in order to becomefamiliar with the tests. After completing the practice session, theywere administered the cognitive and psychological tests. Thirty daysafter their first visit, they completed cognitive and psychologicaltesting again.

Results: A series of repeated measures (ANOVAs) were calculated toexamine the changes between baseline and 30 days administration of thecombination nutraceutical formula and placebo on the cognitive andpsychological measures. As this was the first clinical trial combiningthe three components in the combination nutraceutical formula, we reportthe statistically significant analyses (p<0.05) as well as the analysesapproaching statistical significance (p>0.05≦0.10), which will help thedesign of future studies assessing this compound.

(1) COGNITION: Non-significant changes in simple reaction time, digitvigilance and choice reaction time, spatial working memory and picturerecognition, (long term memory consolidation of objects), were observedover the 30 days administration of the trial. However, 30 daysadministration of the combination nutraceutical formula (compared toplacebo) improved a range of cognitive processes. Means and SDs forthese variables are reported in the table of FIG. 2.

Numeric Working Memory: Participants on the combination nutraceuticalformula treatment showed statistically significant improvement (p>0.03)in numeric working memory accuracy compared to placebo participants. Astatistically significant improvement in holding numbers in workingmemory (immediate memory) was shown from baseline to day 30 due to thecombination nutraceutical formula treatment as shown in FIG. 3.

Spatial Working Memory: There was also a trend towards statisticalsignificance (p<0.09) for the number of outliers during the spatialworking memory task. Outliers indicate lapses in concentration over theduration of the task. Participants in the combination nutraceuticalformula treatment group showed less mean number of such lapses duringthe task and were therefore better able to focus and concentrate/processduring the spatial working memory task, which is a complex cognitivetask.

Word Recognition: The speed of performance during the word recognitiontask was significantly improved (p<0.02) for participants on thecombination nutraceutical formula treatment compared to the placebotreatment over the 30 days of administration (FIG. 1). This indicatedthat the combination nutraceutical formula significantly improved memoryconsolidation processes and in particular, the speed at which aparticipant was able to consolidate and access new memories into longterm storage (FIG. 3). As extensive age related normative data areavailable for the speed of recognition task from the CDR battery, it waspossible to calculate the approximate improvement in relative agerelated functioning due to the combination nutraceutical formulatreatment. An improvement in RT of approximately 100 msec was seen inthe Procera group compared to approximately 20 msec in the placebogroup. Given that the mean age of the group was 48 years, a netimprovement of approximately 80 msec on this task (measuring speed oflong term memory retrieval) equates to approximately the functioning ofage bands some 10-15 years younger (FIG. 4).

(2) MOOD. Depression: The combination nutraceutical formula group showeda decrease in depression scores relative to the placebo group (p<0.06).This suggests that the combination nutraceutical formula may improvedepressive mood conditions.

Anger/Hostility: The combination nutraceutical formula group showed astatistically significant (p<0.03) decrease in anger/hostility over the30 days trial relative to the placebo group. This indicates that 30 daysof treatment with the combination nutraceutical formula significantlyimproves feelings of anger and hostility. This result is supportive ofthe decrease in depression scores.

Confusion: Participants in the combination nutraceutical formula groupalso showed a decrease in confusion over the 30 days trial (p<0.06),which was greater than in the placebo participants. Again, this resultis consistent with the decrease in depression and anger/hostility shownby the combination nutraceutical formula participants over the 30 daystrial. A decrease in confusion may be best understood in terms ofimproving mental clarity.

Vigor: A non-significant change in vigor scores were observed across the30 days of the trial (P<0.10). An improvement in vigor may be bestunderstood in terms of increased mental energy.

Total Mood Disturbance: The main factor score relating to negative moodson the POMS is total mood disturbance. This factor may be regarded as ahighly reliable indicator of changes in negative emotions or moods overthe 30 days of supplementation. There was a highly significant change inthe total mood disturbance over the 30 days in favor of the combinationnutraceutical formula group compared to the placebo group (p<0.02). Thisimprovement in mood due to the combination nutraceutical formula isconsistent with the observed changes in depression, anger/hostility,confusion and vigor. The result also suggests that changes in mood dueto the combination nutraceutical formula are highly noticeable in theparticipants. FIG. 4 displays the changes from baseline over the 30 daystreatment for the combination nutraceutical formula and placebo groups.

Safety: there were no statistical differences in side effects betweenthe two conditions after 30 days of administration.

Alternative Formulation Summary

Remarkably, cognition and mood in healthy participants was not improvedin statistically significant manner or even in a manner approachingstatistical significance. Study design for this formulation wassubstantially as outlined below under the section “AdditionalComparative Examples.”

It should be noted that the overall compositions and respective amountsof ingredients of the comparative composition and contemplatedcompositions were relatively similar, but did produce significantlydifferent results. Indeed, while the comparative composition failed toprovide any measurable advantage (no significant effects on mood, mentalclarity or memory, either working memory or longer term memoryconsolidation or processing speed), or IQ (fluid intelligence),contemplated compositions were statistically significant in a controlledclinical trial. This is especially unexpected as DMAE and selected Bvitamins of the comparative composition were thought to be importantcontributors to and co-factors for a cholinergic enhancement effects ofthe acetyl-l-carnitine and Huperzine A.

Without wishing to be bound by any theory or hypothesis, it iscontemplated that various factors may have contributed to the abovedifference. For example, the comparative composition may over stimulateneuro-cognitive brain cell receptors, in effect undermining cognitivefunction and behavior (e.g., mood). This is often seen withpharmaceutical agents that over stimulate brain cells, thus downregulating receptor sensitivity and/or density in the correspondingneurotransmitter system, or neuro-cognitive brain area. Downregulationin any neurotransmitter system can cause swift and ultimatelydebilitating declines in cognitive and/or psychological (mental health)functions, e.g., memory and mood, respectively.

Moreover, the additional ingredients, even though promising on paper,somehow reduce neural-cognitive function and/or or attenuate or cancelthe Procera effect of the comparative composition. In this context, itshould be noted that there are many putative cognitive enhancers on themarket that claim clinical proof based on presence of multiple activeingredients. Such enhancers will likely suffer from the same drawback asthe comparative composition, or have the active ingredients in minutequantities present that will not have any perceivable effect.

Additional Comparative Examples

Chronometric (brain speed) testing can identify what informationprocessing stage is impacted by the therapeutic agent. This may include:motor reflexes (physical reaction time); perceptual acuity; executivefunction (decision-making speed) and attention; alertness; mentalagility (fluid intelligence), and memory (immediate & delayed).

The following CogCAM™ tests were used: CogCAM 4 Working Memory Speed(decision-making; task-shifting); CogCAM10A Memory Scanning (semantic;letters); CogCAM 10B Memory Scanning (visual-spatial; symbols); CogCAM 1physical reflexes (simple reaction time; attention). These tests provideprimary measures of attention, memory and executive cognitive function.

Inclusion Criteria: Male, and non-pregnant (self reported) femalesubjects, 18 years of age or older, no planned change in lifestyleincluding exercise regimen during study.

Exclusion Criteria: 1. Taking prescription drugs affecting the brain ornervous system within two weeks of study entry (e.g. epilepsy,Alzheimer's disease, Parkinson's disease, anxiety, depression,psychosis, ADD or other psychiatric condition); 2. Taking OTCmedications affecting the brain within two weeks of study entry (e.g.diet pills); 3. Taking supplements known to have an effect on cognitivefunction, memory, anxiety, depression within two weeks of study entry(e.g. Arctic root or Rhodiloa, Ginseng, Gingko, Vinpocetine, 5HTP, St.John's wort, ephedrine (ephedra), phosphatidyl choline, phosphatidylserine, alpha GPC, acetyl-l-carnitine); 4. Smokers.

Formulation C Vinpocetine  20 mg Pantothenic Acid (Vit. B-5) 250 mgDimethylaminoethanol 300 mg Thiamin (Vit. B-1) 250 mg Niacin (Vit. B-3) 20 mg

Formulation E Huperzine A  150 mcg Vinpocetine  20 mg Pantothenic Acid(Vit. B-5) 250 mg Dimethylaminoethanol 300 mg Thiamin (Vit. B-1) 250 mgNiacin (Vit. B-3)  20 mg Acetyl L Carnitine 1000 mg 

Methods and Results

To assess the influence of multiple formulations of Formulation C andEon cognitive function, a battery of web-based tests (the Cognometer)was administered over a 6-week treatment period. An analysis of the datacompared baseline performance to subsequent weekly exams with placebo or1 of 5 formulations taken daily to determine if there was a change incognitive function after initiation of treatment with the dietarysupplement compounds in cognitively intact individuals 18 to 74 years ofage.

Cognitive performance measures were obtained from web-based assessmentsusing the Cognometer test battery subtests; 4-Executive function and10-Immediate Memory. There were 2 treatment groups and one control groupin this study. The group conditions remained blinded in these analyses,the analyses were completed without knowledge of which groups receivedthe test compounds or placebo. Only individuals who completed tests ineach of week (e.g., baseline and all dosing weeks) were included in theanalysis. Outliers who scored more than two standard deviations from themean on a test, and were not internally consistent with other testscores were also eliminated. The elimination of outliers was done toavoid including results that may be due to distractions or web/computerglitches that could invalidate the to particular test session. Analysisof the data uses an analysis of variance (ANOVA) for the differencesbetween the baseline and last week of treatment.

Results and Statistical Analysis

The current trial used the internet to recruit, qualify, register andtest over 1000 subjects with 430 completing the 6 week study. Testingwas conducted at week 0, Baseline, and every subsequent testing andreporting week for 6 weeks during which subjects were administered thetest compounds. On each test day subjects also completed adverse eventforms, questionnaires concerning any changes in lifestyle factors, andcognitive testing.

Following is a description of the Cognometer Tests 4 and 10 used in thetesting of the compounds and the interpretative data and possible claimsthat improvement in these tests represent and support.

Test 4 is a “complex choice reaction time task” that tests so calledexecutive cognitive function, or decision making performance speedmeasured in milliseconds (ms). It has an added unique feature of arandom rule reversing cue which tests both one's ability to rapidlyinhibit one mode of response and switch to another response mode,considered a higher order cognitive function. Facility in “inhibitionand task shifting” can be equated to mental flexibility. Improvement inreaction time on this test supports the claims of: improved mentalquickness and flexibility; improved decision making; improved decisionmaking speed; improved cognitive processing; improved decision makingspeed in a demanding cognitive task.

Test 4 RT data can also be analyzed to assess the group's level offocus, or attention. This measure is derived from computing the standarddeviation of the individual's intra trial reaction times (RTSD). Thisbasically represents the consistency of their responses (processingefficiency) and is considered to reflect the level of sustainedattention. Improved performance on this score, that is RTSD, supportsclaims of: improved attention or focus; improved attention or focus on ademanding cognitive task.

Test 10 is divided into two tests, recognition recall of letters andspatial patterns. Only the visuo-spatial memory part of this test showedsignificance. This test is patterned after the Sternberg Memory Scanparadigm wherein immediate and short term memory processing (scanning &recall) speed equates to memory encoding. Sternberg-like tests, likeCognometer Test 10, have been used for over 30 years in clinical trialsand pharmaceutical research to determine drug effects on memoryprocesses. Improved reaction times on this test support claims of:improved memory; improved memory processing speed; improved encoding ofinformation; improved recall speed.

The most notable, however, statistically insignificant effects werefound in the 35 plus age group, probably suggesting that the compoundsmay be effective in those who are beginning to exhibit normal agerelated slowing associated with increased years of life, typically after30 years of age. Reaction time standard deviation (RTSD) for this testof executive function did not show a significant difference betweengroups. The reaction time median scores (RTmed), a measure of executivefunction (decision making and mental flexibility) did also not indicatesignificant between group differences.

Selected results are as follows, with group A taking placebo, group Ctaking Formulation C, and group E taking C Formulation E.

RT Median - Test 4 Group Mean SEM A 91.509 2.498 C 88.315 2.343 E 94.5052.352

RT Standard Deviation - Test 4 Group Mean SEM A 85.045 5.695 C 89.44.588 E 88.8 5.506

RT Median (Shapes) - Test 10 Group Mean SEM A 91.523 2.016 C 95.6982.797 E 93.103 2.093

Thus, no significant improvement in cognitive functions was observedwith those formulations tested. Such finding is once more remarkable asthe formulations appear to have similar compositions, but significantlydifferent effects in toto.

Ceretrophin Clinical Study and Results

A clinical study was conducted in healthy human participants by theBrain Sciences Institute, Swinburne University in Australia onCeretrophin (see Formulation II above). Approximately 100 participantswere initially enrolled into the clinical study. Human cognition iscomplex but can be measured using standardized tests of informationprocessing, reaction time, attention, concentration, working memory,long term memory and decision making. These standardized measures relateto how human perform simple and complex tasks in real life. By assessinga range of cognitive measures before and after one month administrationof either Ceretrophin or placebo, remarkable results were achieved asprovided in more detail below.

Study Methodology: The study was a randomized, double-blind, placebocontrolled study examining the effects of a special nutritionalformulation Ceretrophin vs placebo on cognitive function and mood. Thismeans that the participants were randomly allocated to either a placeboor Ceretrophin group in which they were administered either placebo orCeretrophin tablets for one month. The study was double blind becauseboth the experimenters and the human participants did not know whichtablets they were taking.

Exclusion Criteria: 1. Not currently taking prescription drugs affectingthe brain or nervous system (e.g., Modafinil, acetylcholinesteraseinhibitors, anti-cholinergics, stimulants, Ldopa, MAO inhibitors, NMDAreceptor antagonists, methylphenidate, amphetamine, pseudo-ephedrine,SSRIs and other anti-depressant medication), 2. Not currently taking OTCmedications affecting the brain (e.g., ephedra based diet pills), 3. Whohave not used any supplements within the past 30 days that have aneffect on cognitive function, memory, anxiety, depression (e.g. Ginseng,Gingko, Vinpocetine, 5HTP, Tryptophan, St. John's Wort, ephedrine(ephedra), alpha GPC, Citicoline, phosphatidylserine,acetyl-l-carnitine, Focus Factora,), 4. Not active Smokers. 5. Nottaking the following: anti-coagulant drugs (Warfarin, Heparin, Plavix);anticholinergics or acetylcholinesterase inhibitors (bethanechol(Ureholine), donepezil (Aricept), rivastigmine (Exelon), galantamine(Reminyl), edrophonium (Enoln, Reversol, Tensilon), neostigmine(Prostigmin) 6. Do not have any of the following health conditions:AIDS, HIV; to Chronic Fatigue Syndrome, Epstein Barr, Fibromylagia,Lupis, Multiple Sclerosis, Thyroiditis, Ulcerative Colitis, Crohn'sDisease, Irritable Bowel Syndrome, dementia including Alzheimer's andParkinsons' disease, Type 1 or 2 Diabetes, Insomnia or Sleep Apnea,Narcolepsy 7. No history of head trauma 8. No neurological deficits 9.Not pregnant or lactating 10. Not anticipating any planned changes inlifestyle (e.g. exercise regimen) for the duration of the study 11. Noknown allergies to nuts 12. Must not be younger than 18 years of age orolder than 65 years of age.

In addition participants were requested not to have alcohol orcaffeine-containing food or beverages on the testing days (e.g., coffee,tea, chocolate and energy drinks containing caffeine or guarana).Further to control for food intake participants they were also requiredto eat a light breakfast (e.g., 2 pieces of toast or cereal with juice)on the testing days.

Test Parameters: The following neuropsychological tests were employed inthe currents study: The Cognitive Drug Research measure (CDR) is awell-validated test, which was used to assess attention, working memoryand episodic secondary (longer term memory, or consolidation).Inspection time (IT) is a measure speed of early information processing.The Profile of Mood States (POMS) is a self-report designed to measuresix dimensions of mood: tension-anxiety; depression-dejection;anger-hostility; vigor-activity; fatigue-inertia; andconfusion-bewilderment (POMS: McNair, Lorr, & Droppelman, 1992).

IQ was assessed using the Raven's Progressive Matrices. This was done byadministering the even items at baseline and the odd items at Week 4.The UWIST Mood Adjective Checklist (UMACL; Matthews, Jones &Chamberlain, 1990) will be used to Measure mood states and energylevels. The Spielberger State-Trait Anxiety Inventory (STAI:Spielberger, 1983) is a 20-item questionnaire, to measure anxiety at thetime of testing. Perceived Stress Scale (PSS; Cohen, 1983) was used tomeasure stress symptoms and effective coping Participants visitedSwinburne University on 3 separate occasions Visit 1: Health assessment,practice, baseline and acute testing Visit 2: 1 week (7 days) followingbaseline testing and Visit 3: 4 weeks (28 days) following baselinetesting. During the first visit, participants completed a general healthassessment and were then allocated into one of three treatment groupsfor baseline and acute testing.

Results

Cognitive Measures: Raven Progressive Matrices (general intelligenceIQ): Participants in the Ceretrophin group statistically improved theirperformance on the Raven Progressive Matrices relative to the placebogroup (p<0.001). This was a very strong effect and equates to an IQimprovement of about 6 IQ points. The Raven Progressive Matrices is awell-validated non-verbal measure of general intelligence. To completethis task a participant must engage in several higher order cognitiveprocesses such as visualisation, spatial working memory, mentalrotation, reasoning, and non-verbal problem solving. This is aremarkable result particularly given the statistical significance andeffect size. This result supports the smaller improvements in accuracyof the less difficult tasks used in the CDR battery. It is of note thatthe most significant effect of Ceretrophin is seen with the most complextask. Future studies may wish to use highly complex cognitive tasks inorder to ascertain the full potential of Ceretrophin on the brain andcognition.

Std. Condition Mean Deviation N Raven's advance progressive Ceretrophin8.2500 3.34984 36 matrix - baseline Placebo 9.3929 3.77457 28 Total8.7500 3.55903 64 Raven's advance progressive Ceretrophin 9.7500 3.4754236 matrix - week 4 Placebo 8.1786 4.49735 28 Total 9.0625 3.99950 64

Simple Reaction Time: The speed of simple reaction time did notsignificantly improve due to the Ceretrophin treatment across the 4weeks of administration. This is the simplest cognitive measure in thecognitive battery. This result is consistent with the results from theother main variables in so far as the Ceretrophin™ did not speed upneural processes but instead improved accuracy and reduced mistakes.

Digit Vigilance and Choice Reaction Time: The Ceretrophin treatmentsignificantly (p=0.05) decreased the number of false alarms (mistakes)during the Digit Vigilance task after 4 week administration.Participants in the Ceretrophin group relative to the placebo groupimproved their attention/concentration. This was a relatively strongeffect.

Std. Condition Mean Deviation N Digit Vigilance - Ceretrophin 1.05131.19095 39 False Alarms - Placebo .6129 1.05443 31 BASELINE Total .85711.14570 70 Digit Vigilance - Ceretrophin .7436 .78532 39 False Alarms -Placebo .7742 1.02338 31 Week 4 Total .7571 .89176 70

Performance on the Choice Reaction Time Accuracy also improved due tothe Ceretrophin™ and this result approached statistical significance(p=0.11). The effects of the Ceretrophin was not to speed up the braindirectly or to make participants quicker to respond to thediscrimination but gave them better accuracy in discriminating betweenthe stimulus alternatives. This indicates an improvement in theefficiency of decision making and information processing. Note thatthere was not a slowing of RT which led to an increase in accuracy. Theincrease in accuracy due to the Ceretrophin was not a consequence of aslowing of response time (increase in RT). Although approachingstatistical significance this was not a strong effect.

Std. Condition Mean Deviation N Choice Reaction Ceretrophin 96.84212.73640 38 Time - Accuracy - baseline Placebo 97.4000 2.58110 30 Total97.0882 2.66394 68 Choice Reaction Ceretrophin 97.3158 2.42849 38 Time -Accuracy - Week 4 Placebo 97.0667 3.51287 30 Total 97.2059 2.93491 68

Spatial Working Memory: There was a trend towards significance forSpatial Working Memory Outliers (p=0.13). Although not significant, theresults (see mean values below) indicate that there was more of animprovement in the number of mistakes over the treatment duration forthe Ceretrophin than for the placebo. Larger sample size may help thisresult become statistically significant. This result should be treatedas a preliminary finding that should be subjected to replication in alarger sample.

Std. Condition Mean Deviation N Spatial Working Memory - Ceretrophin1.0000 1.16190 41 Outliers - baseline Placebo .7813 .83219 32 Total.9041 1.02962 73 Spatial Working Memory - Ceretrophin .7317 1.04939 41Outliers - week 4 Placebo .9063 1.20106 32 Total .8082 1.11377 73

Numerical Working Memory: Participants on the Ceretrophin treatmentshowed an improvement (p=0.18) in Numerical Working Memory Accuracycompared to placebo participants. This again approached statisticalsignificance. The result indicates that there is some evidence thatthere is an improvement in holding numbers in working memory (immediatememory) from Baseline to Week four due to the Ceretrophin treatment.Increasing the sample size (statistical power) may result in thisvariable showing statistical significance. This is an interesting butpreliminary finding.

Std. Condition Mean Deviation N Numeric Working Memory Ceretrophin92.1645 7.24746 38 Original Stimuli - Placebo 95.7787 5.26386 30Accuracy - baseline Total 93.7590 6.65344 68 Numeric Working MemoryCeretrophin 92.6326 7.80322 38 Original Stimuli - Placebo 95.03803.94556 30 Accuracy - week 4 Total 93.6938 6.46620 68

Picture Recognition: There was no significant change in performance inPicture Recognition over the 4 week trial attributable to either Placeboor Ceretrophin treatment.

Word Recognition: Word Recognition Accuracy improved for the Ceretrophinparticipant group but decreased for the Placebo participant group acrossthe 4 weeks of the trial. Although this only approached statisticalsignificance (p=0.12) the results provides some evidence thatCeretrophin treatment improves the accuracy of memory consolidation ofwords. Again a systematic picture of results is emerging with manyvariables showing improvement in accuracy rather than speed, and thatthis improvement in accuracy is not a consequence of a slowing of RT (ormore cautious responding). Overall the changes to the different accuracyvariables suggest that the Ceretrophin improves efficiency by reducingthe number of errors of neural processing of cognitive measures.

Std. Condition Mean Deviation N Word Recognition Ceretrophin 73.333616.25226 36 Original Stimuli - Placebo 74.2534 14.87757 29 Accuracy -baseline Total 73.7440 15.54023 65 Word Recognition Ceretrophin 75.185315.50148 36 Original Stimuli - Placebo 73.1038 14.19566 29 Accuracy -week 4 Total 74.2566 14.85472 65

Inspection Time: A smaller sub-set of participants completed this task.No differences were observed between the Ceretrophin and placebo groupsbut this may be due to the low sample size.

(2) Mood Measures: Perceived Stress (p<0.05): Four week treatment ofCeretrophin showed a small reduction in the levels of stress perceivedby participants relative to the placebo group. It is also noteworthythat participant recruitment did not involve highly stressed or anxiousindividuals but just normal population levels of stress and other moods.This effect may be even more pronounced if a more clinical populationwas tested.

Std. Treatment Mean Deviation N Perceived Ceretrophin 28.2973 3.02641 37Stress Scale Placebo 29.0333 3.87283 30 baseline Total 28.6269 3.4237867 Perceived Ceretrophin 27.4054 3.24431 37 Stress Scale Placebo 29.63333.83705 30 Week 4 Total 28.4030 3.66829 67

Tense Arousal (p=0.12): Consistent with the reduction in the level ofstress, we observed a reduction in the level of tense arousal. This wasnot statistically significant and a larger sample would increase thestatistical power with this variable.

Safety: There were no statistically significant side-effects after 4weeks of testing.

Conclusion of Ceretrophin Study

In terms of the cognitive variables, there is evidence that Ceretrophinimproves functioning during highly complex cognitive tasks that assessgeneral reasoning and problem solving. There was also some evidence thatCeretrophin improved working memory variables. The results if takentogether do also suggest an improvement in the efficiency of informationprocessing and decision making such as in improving accuracy andreducing cognitive errors. The reduction in errors and improvement inaccuracy was seen in nearly all tasks. The highly statisticallysignificant improvement in general intelligence from the RavenProgressive Matrices was larger than the other cognitive variables andso was easily observed statistically (see also Intelligence 39 (2011)100-107, incorporated by reference herein).

In terms of mood, Ceretrophin appears to reduce stress and tension.Given the increase in occupational stress seen throughout the westernworld this is an important finding. Overall the results suggest thatCeretrophin is a unique compound that exerts beneficial effects to bothcognition and mood, particularly in general intelligence and duringcomplex cognitive reasoning tasks/decision making.

Statistically significant improvements in several variables relative toplacebo could be attributed to the 4 week administration of Ceretrophin

-   -   Raven Progressive Matrices (working memory, general        intelligence)    -   Digit Vigilance Errors (attention)    -   Stress (mood)

The study also found some evidence (approaching statisticalsignificance) of the following measures to be improved due to the 4 weekCeretrophin treatment

-   -   Spatial Working Memory Errors (working memory)    -   Numerical Working Memory Accuracy (working memory)    -   Word Recognition Accuracy Original Stimuli (memory        consolidation)    -   Tension (mood)

Thus, specific embodiments of nutritional supplements for enhancingcognitive function have been disclosed. It should be apparent, however,to those skilled in the art that many more modifications besides thosealready described are possible without departing from the inventiveconcepts herein. The inventive subject matter, therefore, is not to berestricted except in the spirit of the appended claims. Moreover, ininterpreting both the specification and the claims, all terms should beinterpreted in the broadest possible manner consistent with the context.In particular, the terms “comprises” and “comprising” should beinterpreted as referring to elements, components, or steps in anon-exclusive manner, indicating that the referenced elements,components, or steps may be present, or utilized, or combined with otherelements, components, or steps that are not expressly referenced.Furthermore, where a definition or use of a term in a reference, whichis incorporated by reference herein is inconsistent or contrary to thedefinition of that term provided herein, the definition of that termprovided herein applies and the definition of that term in the referencedoes not apply.

Procera Extreme Focus (XTF) Composition

The Procera composition as described above includes acetyl-L-carnitine(ALC), vinpocetine and hyperzine A and is also referred to as ProceraAVH. It has been clinically tested successfully as a cognitive and moodenhancer as shown in the examples above. That composition as the ProceraAVH enhances different cognitive functions, including short-term memoryrecall speed, long-term memory, attention (focus and concentration), andmental clarity and mood. The Procera Extreme Focus (XTF) composition aswill be described and referred to as Procera XTF includes those threemajor components of the Procera AVH, plus additional mental performanceboosting, anti-fatigue and anti-stress ingredients, including Rhodiolarosea and key B-vitamins as a Vitamin B complex, including Vitamins B3,B5 and B6. This composition also includes a blend of natural sources ofcaffeine, including a green tea and guarana extract. The caffeine workssynergistically with several of the components in the composition,especially vinpocetine.

The Procera XTF composition combines the clinically validated cognitiveenhancer of the AVH having the acetyl-L-carnitine, vinpocetine andhuperzine A with the benefits of Rhodiola rosea for improved mental andphysical performance under stressful or challenging condition. TheB-vitamins and herbal energy boosting extracts support optimal brainfunction under peak performance demands. It has been found that specificingredients and their concentration and ranges enhance the function ofeach of the ingredients and synergistically helps the brain sustainmental performance longer, including improved concentration, motivation,memory recall and mental energy. The composition is effective for thosepersons that require the additional help of greater brain power andmental and physical energy while studying in the classroom, board roomor participating in an athletic event.

The concentrations and ranges of the AVH ingredients and Rhodiola aregenerally based upon the clinical results explained above. The ProceraXTF is an enhanced and clinically proven composition that includes otheringredients that act synergistically with the AVH components and theRhodiola rosea. Niacin as B3 and pantothenic acid as B5 are disclosed aspart of the composition for Procera XTF, but were not used in theCerotrophin composition. Procera XTF includes the additional B-vitaminsuch as Vitamin B6 that has added neurotransmitter support. Addedcaffeine is supplied from a guarana seed extract and green tea leafextract and other natural caffeine sources such as from coffee aribicaseeds. The caffeine synergistically enhances the vinpocetine. Therhodiola operates as an adaptogen that helps protect the brain fromstress such as from cortisol, and has been shown to have potentanti-depressant and anxiolytic effects most likely due to it's effectson the monoaminergic system acting as an inhibitor of MAO (monoamineoxidase) A and B. The B-vitamins are mainly in support of thecholinergic and serotonergic systems.

The concentrations and ranges of ingredients are similar to thecompositions as described above, but with certain variations that aremade optimal for use with this Procera XTF composition. The examplenutritional supplement composition for enhancing cognitive function thatis formulated as the Procera XTF composition includes theacetyl-L-carnitine, vinpocetine and huperzine A, the B-vitamin complexand the Rhodiola with the natural caffeine sources.

In an example, the Procera XTF nutritional supplement compositionenhances cognitive function and includes at least huperzine A,vinpocetine, acetyl-L-carnitine, and rhodiola. This composition isformulated for oral administration and the huperzine A, vinpocetine,acetyl-L-carnitine, and rhodiola are in a ratio a:b:c:d respectivelysuch that a as the huperzine A is between about 0.8 and 1.2, b asvinpocetine is between about 80 and 120, c as rhodiola is about 1,600and 2,400, and d as the acetyl-L-carnitine is between about 8,000 and12,000. In these examples, the first letters of the alphabet are usedfor the ratios instead of the last letters as previously done as above.

In one example, the composition includes a Vitamin B complex (e) in aratio a:b:c:d:e with the huperzine A, vinpocetine, acetyl-L-carnitine,and rhodiola such that (e) as the Vitamin B complex is between about 700and 1,200. The Vitamin B complex is formed as Vitamins B3, B5 and B6 inan example. In another example a green tea and guarana extract (f) is ina ratio a:b:c:d:f with the huperzine A, vinpocetine, acetyl-L-carnitine,and rhodiola such that (f) as the green tea and guarana extract isbetween about 1,600 and 2,400.

In an example, the rhodiola is formed of about 2 to 4% rosavins and 0.5to 1.5% salidrosides. In another example, the huperzine A,acetyl-L-carnitine, vinpocetine, and rhodiola together account for atleast 80 wt % of a dosage unit of the composition. The huperzine A,vinpocetine, acetyl-L-carnitine, and rhodiola are in a ratio to eachother in another example such that the huperzine A is between about 0.9and 1.1, the vinpocetine is between about 90 and 110, the rhodiola isbetween about 1,800 and 2,200, and the acetyl-L-carnitine is betweenabout 9,000 and 10,000.

In an example, the acetyl-L-carnitine is present in an amount from about1,250 mg to 1,500 mg, the vinpocetine is present in an amount from about10 mg to 30 mg, the rhodiola is present in an amount from about 250 mgto 350 mg, the huperzine A is present in an amount from about 50 mcg to200 mcg, the green tea and guarana extract is present in an amount fromabout 250 mg to 350 mg, and the Vitamin B complex is present in anamount from about 125 mg to 175 mg.

In another example, the composition is formulated with an entericcoating and an inactive ingredient may be selected from the groupconsisting of a carrier, a binder, an excipient, a dye and combinationsthereof. A method of assisting enhancement of cognitive function in aperson is also included by administering the nutritional supplementcomposition.

The Procera XTF nutritional supplement composition enhances cognitivefunction and includes huperzine A, vinpocetine, acetyl-L-carnitine,rhodiola, a Vitamin B complex comprising Vitamins B3, B5 and B6, and agreen tea and guarana extract. The composition is formulated for oraladministration and the huperzine A, vinpocetine, rhodiola,acetyl-L-carnitine, each of Vitamins B3, B5 and B6, and the green teaand guarana extract are in a ratio a:b:c:d:e:f respectively such that aas huperzine A is between about 0.8 and 1.2. B as the vinpocetine isbetween about 80 and 120. C as the rhodiola is between about 1,600 and2,400. D as the acetyl-L-carnitine is between about 8,000 and 12,000. Eas each the Vitamins B3, B5 and B6 is between about 250 to 400. F as thegreen tea and guarana extract is between about 1,600 and 2,400. TheVitamin B3 is formed as Niacin and Niacinamide in one example andVitamin B5 is formed from pantothenic acid and D-calcium pantothenate.

The Procera XTF nutritional supplement composition in an exampleenhances cognitive function and includes huperzine A; vinpocetine;acetyl-L-carnitine; rhodiola; a Vitamin B complex comprising VitaminsB3, B5 and B6; and a green tea and guarana extract. The composition isformulated for oral administration and the huperzine A is present in anamount from about 50 mcg to 200 mcg, and the vinpocetine is present inan amount from about 10 mg to 30 mg. The rhodiola is present in anamount from about 250 mg to 350 mg, and the acetyl-L-carnitine ispresent in an amount from about 1,250 mg to 1,500 mg. Each of VitaminsB3, B5 and B6 are present in an amount from about 40 mg to 60 mg and thegreen tea and guarana extract are present in an amount from about 250 mgto 350 mg. The huperzine A, acetyl-L-carnitine, vinpocetine and rhodiolatogether account for at least 80 wt % of a dosage unit of thecomposition.

The example nutritional supplement composition includes 50 mg of VitaminB3, which is formulated as 25 mg of niacin and 25 mg of niacinamidecorresponding to 250% of a daily value. The composition in the exampleincludes 50 mg of Vitamin B6 as pyridoxine HCL corresponding to a 2,500%daily value. The composition also includes 50 mg of pantothenic acid asD-calcium pantothenate corresponding to 500% of daily value. Theacetyl-L-carnitine is about 1,500 mg per serving. The vinpocetine isabout 15 mg per serving and huperzine A is about 0.15 mg. The Rhodiolarosea is about 300 mg per serving and includes 3% rosavins and 1%salidrosides.

Caffeine is provided by the Guarana seed extract that is 22% caffeine inone example. The green tea leaf extract is 90% caffeine in an example.In another example, the natural caffeine from coffee aribica seeds isabout 90% caffeine. The total composition mixture of the Rhodiola roseaand the Guarana seed and Green tea leaf extract and other ingredients isabout 600 mg. The Guarana seed extract, green tea leaf extract andcoffee blend is about 300 mg, which is equal to about 80 mg of caffeine.

There now follows a description of the various ingredients and theirfunctional workings and synergistic relationship. In use, four capsulesmay be taken 30-60 minutes prior to when needed such as when studyingfor or taking a large exam or to learn something new, such as a computerprogram or application, to be quick and focused at an athletic event orvideo game, or to be sharp and clear headed. Generally, the compositionworks by increasing the circulation of blood to the brain and deliveringthe oxygen, glucose and other nutrients to increase the brain's energyor cerebral metabolism to improve brain function and cognitiveperformance. It also improves key neurotransmitters such asacetylcholine and dopamine to increase sustained focus that is oftendepleted by stress, sleep loss, poor diet and other physical problemsand conditions, including alcohol and aging.

The Procera AVH includes the acetyl-L-carnitine (ALC) that is natural tothe body and is found in fish, which is one reason fish is called brainfood. The human body manufactures some acetyl-L-carnitine, but itdeclines sharply with age. The signs and symptoms of lowacetyl-L-carnitine can be mood swings, memory loss, poor ability tosustain concentration, mental confusion and fatigue. It is an acetylatedform of L-carnitine and is broken down in the blood by plasma esterasesto carnitine to transport fatty acids into the mitochondria forbreakdown and energy production. The acetyl-L-carnitine and food makethe brain more efficient in its energy use.

Vinpocetine is derived from a natural extract found in the periwinkleflower called Vincaminor. It is a neuroprotective antioxidant that helpsprotect the brain against free radicals caused by neurotoxins, stress,alcohol, junk food and aging. It is a semi-synthetic derivative of thealkaloid vincamine as an extract from the periwinkle plant. It mayoperate as a vasodilator and a possible anti-inflammatory agent thatinhibits the up-regulation of NF-kB. It may selectively inhibitvoltage-insensitive NA⁺ channels to result in a dose-dependent decreasein evoked extracellular CA⁺ ions and striatal nerve endings. This mayreduce the neuroinflammatory processes that cause neuronal death or slowdown in chemical transfer in the brain and result in greater brainefficiency.

Huperzine A strengthens memory and addresses the brain's need for theneurotransmitter acetylcholine (ACH) that aids in memory andconcentration. It may offer some brain protection against neurotoxicorganophsophates. It is sesquiterpene alkaloid and is anacetylcholinesterase inhibitor and NMDA receptor antagonist.

The Rhodiola rosea is 3% rosavins and 1% salidrosides. It is a floweringplant that grows in the cold regions of the world and includes 140chemical compounds with its roots containing phenols, rosavin, rosin,rosarin, organic acids, terpenoids, phenolcarbonic acids and theirderivatives, as well as flavonoids, anthraquinones, and alkaloids.Because rosavins is used in the composition at 30%, the Rhodiola willprobably be of Russian origin and may include rosavin, rosarin, androsin. Other active ingredients that may be included within the Rhodiolarosera include rhodioloside and tyrosol with other components showingsome synergy when used with rhodioloside, rosavin, rosarin and rosin.Salidroside is also included and is a polyphenol.

The rhodiola may inhibit MAO-A and MAO-B through a monoamine oxidaseinhibition mechanism. It is believed that the rhodiola promotes therelease of norepinephrine to resist senility. The Rosavin is a cinnamylalcohol glycoside and with salidroside is responsible for antidepressantand anxiolytic actions of the plant. The salidroside is a glucoside ofthe tyrosl found in the rhodiola plant and may be more active thanrosavin. Rhodiola is a potent adaptogen and helps to keep the brain andbody's neurotransmitters and hormones in balance under extreme mentaland physical stress conditions. Rhodiola is also shown to have potentanti-depressant and anxiolytic (anti-anxiety) effects due to itsmodulation of serotonin, norepinephrine and possibly dopamine.

A B-vitamin complex includes Vitamins B3, B5 and B6. These B-vitaminshelp sustain sufficient neurotransmitter levels. Some B-vitamins such asVitamin B5 as pantothenic acid can be depleted by stress and exhaustingmental challenges and raise the need for extra supplementation. TheVitamin B3 includes both niacin and niacinamide. Both are in equalamounts of about 25 mg in one commercial example of the composition.

Niacin is a derivative of pyridine with a carboxyl group (COOH) at the 3position and the corresponding niacinamide has the carboxyl groupreplaced by carboxamide group (CONH) and sometimes other amides andesters. Both niacin and niacinamide are precursors of coenzymesnicotinamide adenine dinucleotide (NAD) and nicotinamide adeninedinucleotide phosphate (NADP). The NAD is important not only incatabolism of fat, carbohydrate, protein and alcohol, but also cellsignaling and DNA repair NADP is operative in anabolism reactions andfatty acid and cholesterol synthesis. Its ability to inhibit cyclicadenosine monosphosphate (CAMP) production and fat breakdown may also bebeneficial in brain function. It is also believed that the niacinamideis an activator of sirtuins to aid in restoring cognition. This could bedue to preventing apoptosis in cells exposed to agents that induceoxidative stress, and thus, may prevent apoptosis in neuronal cells.

Vitamin B5 as pantothenic acid is included and in one example isD-calcium pantothenate to aid in synthesizing coenzyme-A (CoA) andsynthesize and metabolize proteins, carbohydrates and fats. Thedextrorotatory (D) isomer of pantothenic acid possesses the biologicactivity while the levorotatory (L) form may antagonize the effects ofthe other enantiomer. A racemic mixture is usually not preferred. Thecoenzyme-A synthesis is beneficial and acts as an acetyl root carrier toform acetyl-CoA to transport carbon atoms within a cell and operates toincrease energy metabolism for pyruvate to enter the tricarboxylic acidcycle. It is also important for biosynthesizing acetylcholine.

The Vitamin B6 as pyridoxine HCL is used for enzymatic reactiongoverning the release of glucose from glycogen. In vivo, the Vitamin B6is operative with forming the pyridoxal phosphate-dependent enzymes forbiosynethesizing neurotransmitters such as serotonin, dopamine,epinephrine, norepinephrine, and gamma-aminobutyric acid (GABA).

As noted before, there are natural caffeine sources such as the greentea extract and guarana bean extract and natural coffee. Guarana seedscontain about twice the concentration of caffeine found in coffee beanssuch as 2-4.5% caffeine in guarana seeds as compared to 1-2% in coffeebeans. There are many chemicals found in guarana seeds. Primary naturalphenols found in guarana include catechin and epicatechin. Catechin is anatural phenol and antioxidant. The catechin and epicatechin areselective monoamine oxidase inhibitors (MAOI) of the type MAO-B and thusmay reduce the symptoms of Parkinson's Disease and Alzheimer's patients.Epicatechin is able to cross the blood-brain barrier more efficientlythan other agents such as resveratrol, which is more hydrophilic. Thecatechin may activate BDNF pathways.

Green tea extracts offer additional benefits by obtaining differenttypes of tea catechins, epigallocagethin (EGC), epicatechin gallate(ECG), and epicatechin. There are also different flavonoids such askaempferol, quercetin, and myricetin. It is more antioxidant active thanVitamin C such as provided by the EGCG. The green tea extracts havebetter preservation of catechins than black tea extracts and thus are abetter anti-inflammatory. Other types of coffee blends may be usedalthough the caffeine content would be less compared to a guaranaextract, but would have other components and ingredients that may not beincluded in the guarana and green tea extracts. About 300 mg of aguarana and green tea extract (with the optional coffee blend) may beused to equal about 80 mg of caffeine.

The ingredients as described for the Procera XTF have been selected intheir percentage, concentrations and ranges to operate in the mostefficient and best synergistic manner. These percentages, concentrationsand ranges have been developed through extensive experimentation asexplained above and in subsequent trials and experiments. The niacin inVitamin B3 creates vasodilation and imparts some flushing that mayenhance nutrient delivery to the brain and other parts of the body. Theniacinamide in Vitamin B3 contributes to brain energetics at the NADlevel. The NAD exists in an oxidized and reduced form as NAD⁺ and NADHrespectively. The niacin and niacinamide compliment the otheringredients and are selected in a specific range to be effective. The B3and B6 assist for neurotransmitter support with the primaryneurotransmitter as serotonin that operates with the 5-HT₃ receptor. TheVitamin B5 helps synthesize the acetylcholine and may operate as a majorcholinergic enhancer, and thus, the B5 works in synergy for cholinergicenhancement. Some propose that the compromise of the cholinergic systemcauses some Alzheimer's and associated memory loss. Vitamin B5 and itsoperation may be beneficial since the parasympathetic nervous systemuses acetylcholine to send messages. It is believed by some researchersthat neurotransmitter imbalances cause Alzheimer's Disease because of areduced synthesis of acetylcholine. The increased NADH as a result ofthe Procera XTF may result in a six-fold increase in neurotransmitterdopamine and may produce more growth hormone secretion and increase thebody's ability to repair or replace damaged and wounded cells. InParkinson's Disease, the brain cells that produce dopamine die, andthus, the increase in NADH using the composition as described for theProcera XTF may improve patients that have Parkinson's Disease. Thecaffeine from the various sources as described has cognitive enhancingeffects on mental energy and synergistically enhances the effect of thevinpocetine and creates vasodilation and enhances the update and use ofglucose and oxygen.

Through the numerous clinical trials and experiments conducted asexplained above and in subsequent work, the Procera XTF formulation hasbeen found to be effective and the range and concentration ofingredients selected for the most optimal performance in brainenhancement. Other components may be added as experiments continue andfeedback ensues.

Many modifications and other embodiments of the invention will come tothe mind of one skilled in the art having the benefit of the teachingspresented in the foregoing descriptions and the associated drawings.Therefore, it is understood that the invention is not to be limited tothe specific embodiments disclosed, and that modifications andembodiments are intended to be included within the scope of the appendedclaims.

That which is claimed:
 1. A nutritional supplement composition forenhancing cognitive function, comprising: huperzine A; vinpocetine;acetyl-L-carnitine; and rhodiola; wherein the composition is formulatedfor oral administration and the huperzine A, vinpocetine, rhodiola, andacetyl-L-carnitine are in a ratio a:b:c:d respectively such that a asthe huperzine A is between about 0.8 and 1.2, b as the vinpocetine isbetween about 80 and 120, c as the rhodiola is between about 1,600 and2,400 and d as the acetyl-L-carnitine is between about 8,000 and 12,000.2. The nutritional supplement composition of claim 1, comprising avitamin B complex (e) in a ratio a:b:c:d:e with the huperzine A,vinpocetine, rhodiola, and acetyl-L-carnitine such that e as the VitaminB complex is between about 700 and 1,200.
 3. The nutritional supplementcomposition of claim 2, wherein the vitamin B complex comprises vitaminsB3, B5 and B6.
 4. The nutritional supplement composition of claim 1,comprising a green tea and guarana extract (f) in a ratio a:b:c:d:f withthe huperzine A, vinpocetine, rhodiola, and acetyl-L-carnitine such thatf as the green tea and guarana extract is between about 1,600 and 2,400.5. The nutritional supplement composition of claim 1, wherein therhodiola comprises about 2 to 4 percent rosavins and 0.5 to 1.5 percentsalidrosides.
 6. The nutritional supplement composition of claim 1,wherein huperzine A, acetyl-L-carnitine, vinpocetine and rhodiolatogether account for at least 80 wt % of a dosage unit of thecomposition.
 7. The nutritional supplement composition of claim 1,wherein the huperzine A, vinpoceine, rhodiola and acetyl-L-carnitine arein a weight ratio to each other such that the huperzine A is betweenabout 0.9 and 1.1, the vinpocetine is between about 90 and 110, therhodiola is between about 1,800 and 2,200, and the acetyl-L-carnitine isbetween about 9,000 and 10,000.
 8. The nutritional supplementcomposition of claim 1, wherein acetyl-L-carnitine is present in anamount from about 1,250 mg to 1,500 mg.
 9. The nutritional supplementcomposition of claim 1, wherein the vinpocetine is present in an amountfrom about 10 mg to 30 mg.
 10. The nutritional supplement composition ofclaim 1, wherein the rhodiola is present in an amount from about 250 mgto 350 mg.
 11. The nutritional supplement composition of claim 1,wherein the huperzine A is present in an amount from about 50 mcg to 200mcg.
 12. The nutritional supplement composition of claim 1, wherein thegreen tea and guarana extract is present in an amount from about 250 mgto 350 mg.
 13. The nutritional supplement composition of claim 1,wherein the Vitamin B complex is present in amount from about 125 mg to175 mg.
 14. The nutritional supplement composition of claim 1, whereinthe composition is formulated with an enteric coating.
 15. Thenutritional supplement composition of claim 1, further comprising aninactive ingredient selected from the group consisting of a carrier, abinder, an excipient, a dye, and combinations thereof.
 16. A method ofassisting enhancement of cognitive function in a person, comprisingadministering the nutritional supplement composition of claim
 1. 17. Anutritional supplement composition for enhancing cognitive function,comprising: huperzine A; vinpocetine; acetyl-L-carnitine; rhodiola; avitamin B complex comprising vitamins B3, B5 and B6; and a green tea andguarana extract; wherein the composition is formulated for oraladministration and the huperzine A, vinpocetine, rhodiola,acetyl-L-carnitine, each of vitamins B3, B5 and B6, and the green teaand guarana extract are in a ratio a:b:c:d:e:f respectively such thatthe a as huperzine A is between about 0.8 and 1.2, b as the vinpocetineis between about 80 and 120, c as the rhodiola is between about 1,600and 2,400, d as the acetyl-L-carnitine is between about 8,000 and 12000,e as each of the Vitamins B3, B5 and B6 is between about 250 to 400 andf as the green tea and guarana extract is between about 1,600 and 2,400.18. The nutritional supplement composition of claim 17, wherein therhodiola comprises about 2 to 4 percent rosavins and 0.5 to 1.5 percentsalidrosides.
 19. The nutritional supplement composition of claim 17,wherein the Vitamin B3 comprises Niacin and Niacinamide.
 20. Thenutritional supplement composition of claim 17, wherein the Vitamin B5comprises pantothenic acid as D-calcium pantothenate.
 21. Thenutritional supplement composition of claim 17, wherein the compositionis formulated for oral administration such that huperzine A,acetyl-L-carnitine, vinpocetine and rhodiola together account for atleast 80 wt % of a dosage unit of the composition.
 22. The nutritionalsupplement composition of claim 17, wherein the huperzine A, vinpoceine,rhodiola and acetyl-L-carnitine are in a weight ratio to each other suchthat the huperzine A is between about 0.9 and 1.1, the vinpocetine isbetween about 90 and 110, the rhodiola is between about 1,800 and 2,200,and the acetyl-L-carnitine is between about 9,000 and 10,000.
 23. Thenutritional supplement composition of claim 17, wherein theacetyl-L-carnitine is present in an amount from about 1250 mg to 1500mg.
 24. The nutritional supplement composition of claim 17, whereinvinpocetine is present in an amount from about 10 mg to 30 mg.
 25. Thenutritional supplement composition of claim 17, wherein the rhodiola ispresent in an amount from about 250 mg to 350 mg.
 26. The nutritionalsupplement composition of claim 17, wherein the huperzine A is presentin an amount from about 50 mcg to 200 mcg.
 27. The nutritionalsupplement composition of claim 17, wherein the green tea and guaranaextract is present in an amount from about 250 mg to 350 mg.
 28. Thenutritional supplement composition of claim 17, wherein each of thevitamins B3, B5 and B6 is present in an amount from about 40 to 60 mg.29. The nutritional supplement composition of claim 17, wherein thecomposition is formulated with an enteric coating.
 30. The nutritionalsupplement composition of claim 17, further comprising an inactiveingredient selected from the group consisting of a carrier, a binder, anexcipient, a dye, and combinations thereof.
 31. A nutritional supplementcomposition for enhancing cognitive function, comprising: huperzine A;vinpocetine; acetyl-L-carnitine; rhodiola; a vitamin B complexcomprising vitamins B3, B5 and B6; and a green tea and guarana extract;wherein the composition is formulated for oral administration and thehuperzine A is present in an amount from about 50 mcg to 200 mcg, thevinpocetine is present in an amount from about 10 mg to 30 mg, therhodiola is present in an amount from about 250 mg to 350 mg, theacetyl-L-carnitine is present in an amount from about 1,250 mg to 1,500mg, each of Vitamins B3, B5 and B6 are present in an amount from about40 mg to 60 mg and the green tea and guarana extract is present in anamount from about 250 mg to 350 mg, and the huperzine A,acetyl-L-carnitine, vinpocetine and rhodiola together account for atleast 80 wt % of a dosage unit of the composition.
 32. The nutritionalsupplement composition of claim 31, wherein the huperzine A,vinpocetine, rhodiola, acetyl-L-carnitine, each of the Vitamins B3, B5and B6, and the green tea and guarana extract are in a ratio ofa:b:c:d:e:f respectively such that a as the huperzine A is between about0.8 and 1.2, b as the vinpocetine is between about 80 and 120, c as therhodiola is between about 1600 and 2400, d as the acetyl-L-carnitine isbetween about 8,000 and 12,000, e as each of the Vitamins B3, B5 and B6is between about 250 to 400 and f as the green tea and guarana extractis between about 1,600 and 2,400.
 33. The nutritional supplementcomposition of claim 31, wherein the huperzine A, vinpoceine, rhodiolaand acetyl-L-carnitine are in a weight ratio to each other such that thehuperzine A is between about 0.9 and about 1.1, the vinpocetine isbetween about 90 and about 110, the rhodiola is between about 1,800 and2,200, and the acetyl-L-carnitine is between about 9,000 and 10,000. 34.The nutritional supplement composition of claim 31, wherein the rhodiolacomprises about 2 to 4 percent rosavins and 0.5 to 1.5 percentsalidrosides.
 35. The nutritional supplement composition of claim 31,wherein the Vitamin B3 comprises Niacin and Niacinamide.
 36. Thenutritional supplement composition of claim 31, wherein the Vitamin B5comprises pantothenic acid as D-calcium pantothenate.